Signal-transducing Adaptor Protein-2 Regulates Integrin-mediated T Cell Adhesion Through Protein Degradation of Focal Adhesion Kinase.
From: Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Journal of immunology (Baltimore, Md. : 1950)
- Publish Date: Aug 2007
- ISSN: 0022-1767
- Volume: 179
- Issue: 4
- Pages: 2397-407
- Medium: Print
- Language: English
- Citation (JAMA): Sekine Yuichi, Tsuji Satoshi, Ikeda Osamu, et al. Signal-transducing Adaptor Protein-2 Regulates Integrin-mediated T Cell Adhesion Through Protein Degradation of Focal Adhesion Kinase.. J. Immunol. Aug 2007;179:2397-407
Abstract
Signal-transducing adaptor protein-2 (STAP-2) is a recently identified adaptor protein that contains pleckstrin homology- and Src homology 2-like domains as well as a YXXQ motif in its C-terminal region. Our previous studies demonstrated that STAP-2 binds to STAT3 and STAT5, and regulates their signaling pathways. In the present study, we find that STAP-2-deficient splenocytes or T cells exhibit enhanced cell adhesion to fibronectin after PMA treatment, and that STAP-2-deficient T cells contain the increased protein contents of focal adhesion kinase (FAK). Furthermore, overexpression of STAP-2 induces a dramatic decrease in the protein contents of FAK and integrin-mediated T cell adhesion to fibronectin in Jurkat T cells via the degradation of FAK. Regarding the mechanism for this effect, we found that STAP-2 associates with FAK and enhances its degradation, proteasome inhibitors block FAK degradation, and STAP-2 recruits an endogenous E3 ubiquitin ligase, Cbl, to FAK. These results reveal a novel regulation mechanism for integrin-mediated signaling in T cells via STAP-2, which directly interacts with and degrades FAK.
Mesh Headings (Keywords): Adaptor Proteins, Signal Transducing, Amino Acid Motifs, Animals, Cell Adhesion, Fibronectins, Focal Adhesion Kinase 1, Humans, Integrins, Jurkat Cells, Mice, Mice, Knockout, Phosphoproteins, Proteasome Endopeptidase Complex, Proto-Oncogene Proteins c-cbl, STAT2 Transcription Factor, STAT3 Transcription Factor, Signal Transduction, T-Lymphocytes, src Homology Domains
Check for Full Text / PubMed Unique Identifier (PMID): 17675501
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